In vivo monitoring of liver damage using caspase-3 probe.
In vivo monitoring of liver damage using caspase-3 probe.
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作者：
Ozaki M;Haga S;Ozawa T
对细胞和器官状况的实时监测提高了我们对各种生理病理现象的理解。这种监测有望为临床诊断和治疗提供重要的替代方案。我们试图展示器官和细胞的生理病理变化。在这里，我们提出了一个使用基于荧光素酶的caspase-3光学探针对肝脏状态进行体内成像的例子。我们检测了小鼠肝脏和肝细胞凋亡（caspase-3活性）的动态变化，证明发射的信号反映了生化评估的凋亡细胞死亡。在活体肝细胞（AML 12）实验中，检测caspase-3活性的光学探针在fas配体、staurosporine和缺氧/再氧化作用下发出信号，表明该探针可以定量测量细胞凋亡。因此，我们将该探针用于小鼠肝脏缺血/再灌注（I/R）和药物对肝脏的毒性。通过在小鼠肝腺病毒中表达探针，我们在小鼠肝I/R模型中无创和按时间顺序成像肝脏caspase-3活性（即凋亡损伤）。肝缺血持续时间影响缺血后caspase依赖性损伤。缺血（长达60分钟）增强了再灌注后的肝损伤，但长时间缺血（缺血90分钟）诱导的不是凋亡细胞死亡，而是坏死细胞死亡。直接观察器官状况的变化阐明了器官功能和损伤的动态。这些技术显然具有临床意义。它们有望在未来为各种临床环境提供新的诊断工具。
Real-time monitoring of cellular and organ conditions improves our understanding of various physiopathological phenomena. Such monitoring is expected to provide important alternatives for clinical diagnosis and therapy. We have sought to show physiopathological changes of organs as well as cells. Here, we present an example of in vivo imaging of liver states using the luciferase-based caspase-3 optical probe. We examined dynamic changes of apoptosis (caspase-3 activity) of a mouse liver as well as those of liver cells, proving that the emitted signals reflected the biochemically evaluated apoptotic cell death. In live liver cell (AML 12) experiments, the optical probe for caspase-3 activity emitted signals in response to Fas-ligand, staurosporine and hypoxia/reoxygenation, demonstrating that the probe can measure cellular apoptosis quantitatively. We therefore applied this probe for mouse liver ischemia/reperfusion (I/R) and drug-toxicity to liver. By expressing the probe in a mouse liver adenovirally, we imaged liver caspase-3 activity (i.e. apoptotic damage) non-invasively and chronologically in the hepatic I/R model of mice. The duration of liver ischemia affected the post-ischemic caspase-dependent damage. Ischemia (up to 60 min) enhanced liver damage after reperfusion, but prolonged ischemia (90 min of ischemia) induced not apoptotic cell death but necrotic cell death. Direct observations of the changes of organ conditions elucidated the dynamism of organ function and damage. These technologies clearly possess clinical relevance. They are expected to provide a new diagnostic tool for various clinical settings in the future.
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影响因子：
12.4
作者：
Yhee JY;Kim SA;Koo H;Son S;Ryu JH;Youn IC;Choi K;Kwon IC;Kim K
通讯作者：
Kim K
DOI：
10.1158/1078-0432.ccr-07-5244
发表时间：
2008-09-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ray P;De A;Patel M;Gambhir SS
通讯作者：
Gambhir SS
影响因子：
12.4
作者：
Kim GB;Kim YP
通讯作者：
Kim YP
体内蛋白酶表达的实时视频成像
影响因子：
12.4
作者：
Zhu L;Xie J;Swierczewska M;Zhang F;Quan Q;Ma Y;Fang X;Kim K;Lee S;Chen X
通讯作者：
Chen X
影响因子：
15.9
作者：
Faubion, WA;Guicciardi, ME;Gores, GJ
通讯作者：
Gores, GJ